The U.S. Food & Drug Administration announced Nov. 26 that it has approved Zimeta (dipyrone injection) for the control of fever (known as pyrexia) in horses.
According to FDA, Zimeta belongs to the pyrazolone class of non-steroidal anti-inflammatory (NSAID) drugs and is the first injectable dipyrone product to receive FDA approval for use in horses.
Zimeta is a prescription animal drug product containing 500 mg of dipyrone per milliliter and is intended for intravenous injection once or twice daily (every 12 hours) for up to three days, FDA said. As a class, NSAIDs may be associated with adverse effects on the gastrointestinal system, kidneys and liver and a decreased ability to form blood clots (coagulopathy), FDA explained, noting that Zimeta has been shown to cause gastric ulcers, abnormal feces and prolongation of coagulation parameters in horses. Horses on Zimeta should be monitored for signs of lack of appetite, diarrhea or unexplained bleeding. In addition, caution should be used in horses at risk for hemorrhage, the agency added.
Zimeta is for use in horses only. The safe use of Zimeta has not been evaluated in horses under three years of age, horses used for breeding or pregnant or lactating mares. Zimeta is not for use in horses intended for human consumption or for use in food-producing animals, including lactating dairy animals, due to safety concerns for humans, FDA said.
Zimeta is not for use in humans. Direct contact with the skin should be avoided. Practitioners should employ precautions when handling and using loaded syringes to prevent accidental self-injection, as studies have indicated that dipyrone can cause agranulocytosis, a serious and potentially life-threating condition in which there is a white blood cell deficiency that can increase a person’s vulnerability to infection.
In 1977, FDA formally withdrew the approval of all dipyrone-containing drugs intended for use in humans after becoming aware of reports of agranulocytosis in treated patients, the agency said. Dipyrone is now prohibited for use in humans in several countries. However, FDA said the data generated to support the approval of Zimeta did not indicate that agranulocytosis occurred in horses treated with the drug.
Following the removal of the human drug product from the U.S. market, sales of an unapproved equine dipyrone product continued. However, in 1996, FDA removed the unapproved equine dipyrone product from the market due to concerns about its use in food-producing animals, the agency said. Subsequently, FDA noted increased distribution of compounded dipyrone sold for use in horses.
FDA cautioned veterinarians, animal caretakers and animal owners about the use of unapproved, compounded drugs that have not been evaluated for safety and effectiveness. These unapproved products may vary in quality, potency and bioavailability.
FDA-approved drugs have been demonstrated to be safe and effective for their intended use and have been consistently manufactured to preserve the drugs’ identity, strength, quality and purity. After FDA approval, the agency also continues to monitor the safety, efficacy and manufacturing of the drug. Safety monitoring includes the evaluation of post-approval adverse reactions. Unapproved drugs, including compounded drugs, do not undergo the same pre-approval and post-approval evaluations.
In the announcement, FDA strongly encouraged use of an FDA-approved dipyrone animal drug product, when dipyrone is indicated, for the control of pyrexia in horses.
As with all approved animal drugs, FDA said it will monitor and evaluate submitted adverse event reports for Zimeta, which would include monitoring for potential human safety risks associated with dipyrone and indications that the product is being used in an extra-label manner in food-producing animals.
Zimeta is manufactured by Kindred Biosciences Inc., based in Burlingame, Cal.